The study was conducted by Pedro Reche and Derin Keskin from the Dana-Farber Cancer Institute, Boston, USA and other colleagues from Dana-Farber and Harvard Medical School, Boston, USA. They used bioinformatics techniques to predict which HIV-1 protein fragments - or 'epitopes' - were likely to trigger a response from immune system cells called cytotoxic T lymphocytes. They identified 37 epitopes. Reche, Keskin et al. then predicted which of these 37 epitopes were likely to be recognised by most people's immune systems, taking into account genetic differences in immune system genes, called HLA genes, depending on ethnic origin. They identified 25 epitopes, which they combined into five pools with which to test immune responses. They predicted that only 5 of these epitopes would be recognised by over 95% of people's immune systems.
The authors exposed cultured lymphocytes from HIV-1 infected patients to the epitope pools, and repeated the experiment with cultured lymphocytes from healthy donors. They assessed the response to the epitopes by measuring the levels of interferon gamma (IFN gamma) produced by the cultured T lymphocytes - IFN gamma is produced by responsive T lymphocytes upon activation by pathogenic or viral proteins and helps to destroy infectious organisms.
Reche, Keskin et al.' s results show that only a small proportion of cells from HIV-1infected patients recognised the epitopes and mounted an adequate immune response: cells from only 31-45% of patients produced IFN gamma, and in small quantities. By contrast, cells from all healthy donors responded and produced IFN gamma in large quantities. The authors also demonstrate that these exposed lymphocytes from uninfected individuals could kill HIV-1 infected cells.
Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes
Pedro A Reche, Derin B Keskin, Rebecca E Hussey, Petronela Ancuta, Dana Gabuzda and Ellis L Reinherz
Medical Immunology 2006, (in press)
After the embargo, article available from the journal website at:
This article is accompanied by an editorial available from the journal website after the embargo